Histone Ubiquitination: An Integrative Signaling Platform in Genome Stability

Francesca Mattiroli; Lorenza Penengo

doi:10.1016/j.tig.2020.12.005

Histone Ubiquitination: An Integrative Signaling Platform in Genome Stability

Trends Genet. 2021 Jun;37(6):566-581. doi: 10.1016/j.tig.2020.12.005. Epub 2021 Jan 20.

Authors

Francesca Mattiroli¹, Lorenza Penengo²

Affiliations

¹ Hubrecht Institute-KNAW and University Medical Center Utrecht, 3584CT Utrecht, The Netherlands.
² Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland. Electronic address: penengo@imcr.uzh.ch.

PMID: 33485674
DOI: 10.1016/j.tig.2020.12.005

Abstract

Complex mechanisms are in place to maintain genome stability. Ubiquitination of chromatin plays a central role in these mechanisms. The ever-growing complexity of the ubiquitin (Ub) code and of chromatin modifications and dynamics challenges our ability to fully understand how histone ubiquitination regulates genome stability. Here we review the current knowledge on specific, low-abundant histone ubiquitination events that are highly regulated within the cellular DNA damage response (DDR), with particular emphasis on the latest discovery of Ub phosphorylation as a novel regulator of the DDR signaling pathway. We discuss players involved and potential implications of histone (phospho)ubiquitination on chromatin structure, and we highlight exciting open questions for future research.

Keywords: DDR; DNA damage response; H2AK15ub; RNF8/RNF168/USP51; chromatin modifications; pUbT12; ubiquitin phosphorylation.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
DNA Damage
DNA Repair
Genomic Instability*
Histones / genetics
Histones / metabolism*
Humans
Methylation
Phosphorylation
Ubiquitin / genetics
Ubiquitin / metabolism*
Ubiquitination

Substances

Histones
Ubiquitin